1092789-19-9Relevant academic research and scientific papers
Crystal structures of PI3Kα complexed with PI103 and its derivatives: New directions for inhibitors design
Zhao, Yanlong,Zhang, Xi,Chen, Yingyi,Lu, Shaoyong,Peng, Yuefeng,Wang, Xiang,Guo, Chengliang,Zhou, Aiwu,Zhang, Jingmiao,Luo, Yu,Shen, Qiancheng,Ding, Jian,Meng, Linghua,Zhang, Jian
supporting information, p. 138 - 142 (2014/03/21)
The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3Kα-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3Kα-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3Kα inhibitors.
2-ARYLNAPHTHYRIDIN-4-ONES AS POTENT ANTITUMOR AGENTS TARGETING TUMORIGENIC CELL LINES
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Page/Page column 9; 15, (2014/11/13)
In order to search for new antitumor drug candidates from 2-arylnaphthyridin-4-ones (ANs), we have designed and synthesized a series of 3 '-hydroxy or 6-hydroxy derivatives of ANs. Following the antitumor activity screening, most of these compounds were found to exhibit significant activity. Among them, 2-(3-hydroxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (67) was the most promising. In a preliminary action mechanism study, the treatment of Hep3B hepatoma cells with compound (67) reveals that its mechanism of action is affect on microtubule and metastasis-related proteins. Then, the corresponding phosphate prodrug (86) of compound (67) was tested against Hep3B xenograft nude mice model for antitumor activity.
Kinase antagonists
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Page/Page column 21, (2008/06/13)
The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tryosine kinase, PI3Kinase and mTOR, or PI3Kinase, mTOR and tryosine kinase.
